The overall objective of the proposed research is to understand the 3-dimensional dynamic geometry, and regional and global systolic mechanics of the human LV and RV in the context of cardiac disease and therapeutic interventions. Four interrelated projects will extend this work into promising, clinically relevant areas. This effort will take advantage of the unique capabilities of the myocardial marker technology to determine the 3-D instantaneous motion of multiple fixed intramyocardial sites in the hearts of intact human subjects and experimental animals. Project I investigates "Valvular-Ventricular Interaction". Despite experimental evidence and clinical suggestions that preservation of the mitral chordae tendineae optimizes LV systolic function, MVR with excision of the subvalvular apparatus remains the standard procedure, and the mechanism whereby preservation of the chord is responsible for this salutary effect remains totally unknown. A series of animal and human protocols will address 6 hypotheses to elucidate the functional basis for this phenomenon (and the effects of rigid [prosthetic ring] annular fixation) in terms of 3-D dynamic LV geometry, local finite deformations, regional radii of curvature, and regional and global systolic LV mechanics. Project II examines the mechanisms of mitral regurgitation due to regional LV ischemia, the 3-D dynamics of direct intraventricular mechanical coupling (mechanical linkage) between ischemic and nonischemic areas, and the relationships between regional and global LV systolic performance. Three hypotheses will be tested in animal experiments and corroborated in patient studies. Project III addresses two hypotheses in animal and human experiments to determine: 1) The effects of (temporary or permanent) LVAD circulatory support on interventricular septal shifting and resultant RV/LV geometry changes, regional and global RV systolic mechanics, and septal contraction; and, 2) The effects of acute RV pressure overload on septal shifting, regional LV systolic mechanics, finite deformations, and dynamic 3-D geometry.Project IV is directed towards mapping, for the first time in the human LV, regional finite deformations and radii of curvature throughout the cardiac cycle. Regional principal correlated with regional transmural finite deformations to understand better the relation between LV anatomy and dynamics. The effects on regional strains and curvatures of alterations in preload, afterload, contractility, ventricular excitation sequence, and septal geometry (accompanying alterations in transseptal pressure gradients) will be examined. The studies have important implications for the understanding of the geometric design, shape, and functional dynamics of the human ventricular myocardium in both health and disease.